Hsp 90 is critical for cell survival and appears to be important for the maturation of a set of proteins, notably certain transcription factors and kinases. The determination of the range of proteins that it interacts with as well as the means by which it assists proteins to mature are the primary objectives of this study. The extent of interaction with newly synthesized proteins (proteins in the process of maturation) will be determined in whole cell lysates as well as fractionated polysomes. In order to follow the interactive process of hsp 90, in vitro translation of a known substrate, the androgen receptor, will be focused on using both the wild type protein as well as a mutant form of the receptor involved in disease. Here we plan to exploit the fact that the AR represents a co-called 'glutamine expansion' protein associated with neurological disease (ie. spinal/bulbar muscular atrophy). A number of neurodegenerative disease (the best known being Huntingtons disease) are known to arise due to expanded CAG trinucleotide repeats that encode runs of glutamine residues. We anticipate these studies will provide new insights on the still unresolved function of hsp90. In addition we believe the second part of our studies will help us begin to understand the possible connection between molecular chaperones and the pathway by which glutamine expansion proteins undergo misfolding, aggregation and/or degradation.